ALBERT

Description: In the continuous permafrost zone, unfrozen ground may exist beneath large lakes and streams. Sub-lake taliks that extend through permafrost provide a potential conduit for subpermafrost groundwater to reach the surface, increasing dissolved ion concentrations in lake water. Twenty-eight lakes on the Arctic Coastal Plain of northern Alaska were sampled in 2013–14 to determine whether a difference in ionic concentration could be detected between lakes with and without through taliks. A thermal model originally developed by J. Ross Mackay indicated that 20 of the lakes may have a talik that penetrates the permafrost. Lake water samples were analysed for a variety of ions and geochemical properties. Generally, there was little interannual variation in ion concentration, pH and specific conductivity of lake water. Proximal lakes tended to have similar chemical signatures, but there were large variations across the study region. Local factors appeared largely to control lake water chemistry. Lakes with suspected through taliks did not demonstrate a hydrochemical signature distinct from nearby lakes lacking a through talik. This suggests that either: (1) there is no hydrological connection with subpermafrost groundwater due to aquicludes in the subsurface; (2) the flux of groundwater is too small to have a measurable impact on lake water chemistry; or (3) the steady-state condition for talik configuration assumed in the thermal model is not justified. Copyright © 2016 John Wiley & Sons, Ltd.

Description: Abstract 886 Patients with chronic lymphocytic leukemia (CLL) having del(17p13.1), complex karyotype, or fludarabine-refractory disease have few therapeutic options. The cyclin-dependent kinase (CDK) inhibitor flavopiridol (Alvocidib) has been demonstrated to be very effective in genetically high-risk and fludarabine-refractory CLL cases, with a response rate of approximately 50%. We pursued pre-clinical and now early clinical studies of SCH 727965. SCH 727965 is a selective inhibitor of CDK 1, 2, 5 and 9 (IC50 of 〈 5nM) that shows in vitro and in vivo anti-tumor activity in a variety of pre-clinical models. Notably, SCH 727965 has an improved therapeutic index over other CDK inhibitors such as flavopiridol. A solid tumor phase I study with SCH 727965 administered by 2-hour IV infusion on days 1, 8 and 15 of a 28-day cycle has been completed, resulting in a recommended phase II dose of 12 mg/m2. Our pre-clinical studies with SCH 727965 demonstrate potent induction of apoptosis in CLL patient cells following a 2-hour incubation, with an LC50 of 240 nM. This effect is independent of prior treatment status, IgVH gene mutational status, and high-risk cytogenetic abnormalities. Importantly, minimal cytotoxicity toward normal T cells is observed. Similar to other CDK inhibitors in CLL, SCH 727965 promotes rapid down-regulation of the pro-survival gene MCL1 at both the mRNA and protein levels. Stimulation of CLL cells with CD40L mimics the lymph node microenvironment and increases resistance of CLL cells to drug-induced apoptosis (Smit et al., Blood 109:1660-68, 2007). However, co-treatment of CLL cells with SCH 727965 plus CD40L does not abrogate the apoptotic effect of SCH 727965. Based upon these promising data, a disease-specific phase I study of SCH 727965 has been initiated in previously treated CLL patients. This trial started at a dose level below the phase II dose established in the solid tumor study, due to the previous observation of hyperacute tumor lysis in CLL with other CDK inhibitors. SCH 727965 is administered by 2-hour IV infusion on days 1, 8 and 15 of a 28-day cycle. Dosing cohorts are: 5 mg/m2, 7 mg/m2, 10 mg/m2, and 14 mg/m2. Further dose-escalation is allowed, depending on the frequency of dose limiting toxicities observed. To date, we have completed enrollment to cohorts 1 and 2 of the study, with ten patients enrolled. Clinical features of the patients include a median age of 58 (range 43 to 73), 60% Rai stage 3 or 4, and 60% with high-risk genomic features (del17p13, del11q22, or more than two abnormalities). These patients received a median of six (range 1 to 12) prior therapies, and 90% received prior fludarabine therapy. Biochemical evidence of tumor lysis (increased potassium, phosphate, or LDH) post-treatment has been observed in three patients. Common toxicities observed include: nausea, vomiting, diarrhea and fatigue. One patient with pre-treatment neutropenia developed fatal bacterial sepsis during cycle 1 of therapy. Three patients have discontinued therapy due to progressive disease after cycle one, including one patient who died from CLL disease. Two patients discontinued therapy with stable disease. Four patients remain on therapy; one in the lowest dose cohort has demonstrated a partial response by IWCLL 2008 criteria. The other three patients currently are early in the course of planned therapy. The clinical observation of rapid improvement in palpable adenopathy after SCH 727965 treatment is consistent with the laboratory observation of continued sensitivity of CD40L-exposed CLL cells to SCH 727965. Pharmacodynamic studies demonstrate down-modulation of MCL1 in a subset of patients. These data provide promising pre-clinical, and now early clinical, evidence of the potential therapeutic benefit of SCH 727965 in CLL. Dose escalation of SCH 727965 continues and updated results will be presented. This work was supported by the D. Warren Brown Foundation and Specialized Center of Research from the Leukemia and Lymphoma Society. Disclosures: Small: Schering Plough: Employment. Statkevich:Schering Plough: Employment. Bannerji:Schering-Plough: Employment.

Description: Introduction: Abnormalities of cell cycle regulation have an important role in the pathogenesis of cancers. Cyclin dependent kinase (CDK) inhibitors have shown potent activity in patients with chronic lymphocytic leukemia (CLL) and other cancers. Dinaciclib (MK-7965/SCH 727965) is a novel, selective inhibitor of CDK1, CDK2, CDK5, and CDK9. Prior studies show that dinaciclib has anti-leukemic activity against CLL. The present study compared the efficacy and safety of dinaciclib with ofatumumab in patients with refractory CLL. Methods: This Phase 3 randomized, open-label, active-controlled, balanced, multi-site, group sequential confirmatory trial evaluated the progression-free survival (PFS; primary objective), overall response rate and overall survival (secondary objectives), and safety of dinaciclib vs. ofatumumab in patients with refractory CLL. Patients with a confirmed diagnosis of CLL (based on 2008 International Workshop on CLL criteria) and fludarabine or chemoimmunotherapy refractory disease were enrolled if they had no central nervous system involvement, prior allogenic bone marrow transplant or uncontrolled autoimmune anemia or thrombocytopenia. Patients previously treated with dinaciclib, ofatumumab, or other CDK inhibitors were excluded. In Cycle 1, dinaciclib was administered intravenously (IV) over 2 hours at doses of 7 mg/m2 on Day 1, 10 mg/m2 on Day 8 and 14 mg/m2 on Day 15. In Cycle 2 and thereafter, dinaciclib was dosed at 14 mg/m2 on Days 1, 8, and 15 of each 28-day cycle for a total of 12 cycles. Ofatumumab was administered IV once-weekly for 8 weeks starting in Cycle 1 on Day 1, followed by 9 monthly doses as follows: 300 mg in Cycle 1 on Day 1; 2000 mg in Cycle 1 on Days 8, 15, and 22, Cycle 2 Days 1, 8, 15, and 22, and 5 weeks later on Day 1 of Cycles 4-12. Efficacy results are from the intent to treat (ITT) population, and safety results are from the all-subjects-as-treated population. Results: In total, 44 patients were randomized (ITT) and 42 were treated (20 dinaciclib and 22 ofatumumab) due to early study termination not attributed to safety. At study entry, the median age was 62 years (range, 43-77), 32/42 (76.2%) patients were male, 26/42 (62.0%) were RAI stage III-IV, 24/42 (57.1%) had bulky disease, 40/42 (95.2%) were ECOG ≤ 1, the median number of prior therapies was 3 (range, 1-20), and 39/42 (92.9%) patients received prior fludarabine. Deletion 17p (del 17p) was present in 17/42 (38.6%) patients, 7 dinaciclib and 10 ofatumumab. Median follow-up (range) was 16.7 (0.4-26.1) months. In the dinaciclib and ofatumumab groups, respectively, 11 (55.0%) and 17 (70.8%) patients had PFS events, and median (95% CI) PFS was 59.7 (45.0, 92.1) and 25.7 (9.3, 40.7) weeks. Overall response (all partial responses) was recorded for 8 (40.0%) dinaciclib and 2 (8.3%) ofatumumab patients. Stable disease was achieved by 7 (35.0%) dinaciclib and 11 (45.8%) ofatumumab patients. Median survival (95% CI) was 21.2 (16.6, NR) months with dinaciclib and 16.7 (2.3, 20.2) months with ofatumumab; 6 (30.0%) and 11 (45.8%) patients have died in each group, respectively. There were 2 treatment-related deaths in the dinaciclib arm (pneumonia and febrile neutropenia) and none in the ofatumumab arm. Median survival (95% CI) in the del 17p population was 21.2 (1.4, 21.2) months with dinaciclib and 5.4 (0.4, NR) months with ofatumumab. Overall, 17 (85.0%) dinaciclib and 13 (59.0%) ofatumumab patients had a grade 3-5 adverse event (AE). The most common grade ≥ 3 AEs with dinaciclib and ofatumumab, respectively, were neutropenia, 7 (35.0%) vs. 2 (9.1%); thrombocytopenia, 4 (20.0%) vs. 2 (9.1%); decreased neutrophil count, 4 (20.0%) vs. 1 (4.5%); pneumonia, 1 (5.0%) vs. 3 (13.6%); sepsis, 1 (5.0%) vs. 3 (13.6%); and febrile neutropenia, 2 (10.0%) vs. 1 (4.5%). One dinaciclib patient developed tumor lysis syndrome that was deemed not treatment-related. Ten (50.0%) dinaciclib and 13 (54.2%) ofatumumab patients discontinued from the study for the following reasons: AE, 3 (15.0%) vs. 1 (4.2%); disease progression, 4 (20.0%) vs. 4 (16.7%); death, 1 (5.0%) vs. 5 (20.8%); and other/unknown, 2 (10.0%) vs. 4 (16.7%). Conclusion: The limited data from this study demonstrate potential anti-cancer activity and tolerability of dinaciclib compared with ofatumumab in patients with refractory CLL. Based on these results and given the distinct mechanism of action, combinations of dinaciclib with other novel therapies should be explored. Disclosures Ghia: Janssen: Consultancy; Acerta Pharma BV: Research Funding; Adaptive: Consultancy; Pharmacyclics: Consultancy; Roche: Consultancy, Research Funding; AbbVie: Consultancy; Gilead: Consultancy, Research Funding, Speakers Bureau; GSK: Research Funding. Pathiraja:Merck & Co., Inc.: Employment, Other: stock/stock options. Derosier:Merck & Co., Inc.: Employment, Other: stock/stock options. Small:Merck & Co., Inc.: Employment, Other: stock/stock options.

Description: Chronic Lymphocytic Leukemia (CLL) is the most common leukemia in adults. While the breadth of therapies for this incurable disorder has increased recently, patients afflicted with high risk disease have few and predominantly unsatisfactory options. Cyclin-dependent kinase (CDKs) inhibitors, such as Flavopiridol, have demonstrated clinical activity in CLL, though have been associated with significant therapy associated tumor lysis (TLS). Dinaciclib is a selective inhibitor of CDKs 1, 2, 5, and 9 that exhibits activity in CLL, including high risk subtypes. We performed a phase 1 dose escalation trial in relapsed and refractory CLL in order to determine the recommended phase 2 dose and maximum administered dose of dinaciclib. Patients received treatment as a 2-hour IV infusion on days 1, 8 and 15 of a 28-day cycle. The initial starting dose, determined based on preclinical data, was 5 mg/m2. Other dosing cohorts of 7 mg/m2, 10 mg/m2, 14 mg/m2 and 17mg/m2 were included in the dose escalation schema. An expansion cohort of patients utilizing an intra-patient dose escalation of 7mg/m2 on day 1, 10mg/m2 on day 8 and 14mg/m2 on day 15 during cycle 1 and 14mg/m2 on days 1, 8, and 15 of each subsequent cycle was further employed. Patients continued on treatment until there was disease progression, unacceptable toxicity or subject’s refusal to continue. In total, 52 patients have been enrolled on this trial. The median age is 62.4 years (range 43-79), with 46% of patients ≥65 years. The majority of patients have advanced Rai stage (65%) and/or bulky disease (69%) and 46% with del(17p13.1). The median number of prior therapies is 4 (range 1-12) with 92% having received prior fludarabine and 31% having received prior flavopiridol. One episode of a dose limiting toxicity (DLT) was noted at 7mg/m2 (sepsis/death) and two at dose level of 17mg/m2 (hyperacute tumor lysis syndrome and pneumonia). One further DLT of TLS occurred at the recommended phase II dose level of 14mg/m2 during cohort expansion for a total of 18 patients treated at 14mg/m2. The most common serious adverse events included leucopenia, anemia, thrombocytopenia and metabolic evidence of tumor lysis, which occurred in 15% of patients. Clinical response was assessed utilizing the 1996 NCI-WG CLL criteria. The overall response rate of evaluable patients was 58% (28 of 48), while 57% patients with del(17p13.1) and 63% with del(11q22) achieved at least a partial response. The median progression free survival was 481 days (95% CI, 253 – 481). For responders, the median treatment duration was 214.5 days (range, 79 – 470 days). In conclusion, Dinaciclib is clinically active in this population of relapsed and refractory CLL. Importantly, patients with high risk disease, such as del(17p13.1) demonstrated impressive overall responses. Utilizing a dose escalation treatment model, Dinaciclib is well tolerated, safe and associated with typical toxicities which are readily managed. The use of this agent in combination with other efficacious agents, especially in the high risk CLL population is warranted. Disclosures: Jones:Pharmacyclics: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Small:Merck: Employment. Im:Merck: Employment. Zhou:Merck: Employment.

Description: Abstract 3287 Background: Dinaciclib is a potent and selective inhibitor of the CDKs 1, 2, 5, and 9 that has demonstrated anti-tumor activity against both myeloid and lymphoid leukemia cell lines in vitro and human tumor xenografts in vivo. Methods: A randomized, multicenter, open-label phase 2 study of dinaciclib 50 mg/m2 administered by 2-hour i.v. infusion once every 21 days was initiated with the goal of assessing its efficacy and safety in patients (pts) with advanced acute myeloid (AML, ≥60 years old) or lymphoid (ALL, ≥18 years old) leukemia. AML pts were randomized between dinaciclib and gemtuzumab ozogamicin (GO) with cross-over to dinaciclib if no response to GO, while ALL pts only received dinaciclib. Intra-patient dose escalation of dinaciclib to 70 mg/m2 in cycle 2 was allowed. Twenty-six pts were treated on study (20 AML, 6 ALL). Data on 14 AML (2 cross-over from GO) and 6 ALL pts treated with dinaciclib are presented. Their median age was 70 (range 38–76) years and 70% were male. Sixteen pts were refractory and 4 pts had relapsed after a median of one (range 1–4) chemotherapy regimens. Four AML pts had complex karyotypes (≥3 abnormalities), 2 monosomy 7, 2 trisomy 8, 1 der (1:7)(q10;p10), 1 trisomy 21, 1 deletion 9q, and 3 had normal karyotype. Two ALL pts had t(9;22). Response: Anti-leukemia activity was observed in 60% of pts. Ten of 13 pts with circulating blasts (7/7 AML and 3/6 ALL) had 〉50% and 6 pts (4 AML, 2 ALL) 〉80% decrease in the absolute blast count (ABC) within 24 hours of the first dinaciclib dose. An additional pt had a 29% decrease in ABC. The median pre-treatment ABC was 1085 (range 220–9975) and the median ABC nadir was 169 (range 0–1350). The median duration of blast nadir was 6 days (range 2–23). A representative graph from an AML patient (below) shows a rapid decrease of circulating blasts and WBC after treatment, followed by a gradual recovery. Two patients had 〉50% reduction of marrow blasts (35% on d1 to 17% on d 42 in an AML pt; 81% on d1 to 27% on d 21 in an ALL pt). However, no objective responses by International Working Group criteria were observed. The median number of treatment cycles was 1 (range 1–5), with 10 pts receiving more than one cycle of treatment. Eight pts were treated with dinaciclib 70 mg/m2 starting in cycle 2. Toxicity: Treatment related AE's occurring in 〉30% of pts included diarrhea, nausea, vomiting, anemia, elevated AST, fatigue, leukopenia, hypocalcemia, and hypotension. The most common CTCAE v3 treatment-related grade 3 and 4 toxicities, occurring in 3 or more pts, were anemia, leukopenia, febrile neutropenia, thrombocytopenia, fatigue, increased AST, and tumor lysis syndrome (TLS). Laboratory evidence of tumor lysis in cycle 1, using the Cairo-Bishop criteria, was seen in 6 pts in addition to 3 pts with clinical TLS (JCO 2008;26:2767). Hyperacute TLS requiring hemodialysis occurred in one pt with AML, who died of acute renal failure. Subsequently, all pts were aggressively managed to prevent and treat TLS (hospitalization, hydration, allopurinol, rasburicase, oral phosphate binder administration, and early management of hyperkalemia). An additional 9 pts died on study, 8 pts from leukemia progression and 1 pt from intracranial bleed due to disease-related thrombocytopenia. Pharmacodynamics: Pre-treatment, 4 and 24 hrs post end-of-infusion samples of circulating leukemic blasts were obtained from 1 AML and 3 ALL pts. By Western blot, post-treatment decrease in Mcl-1 and increase in PARP cleavage were seen in all 4 pts at 4 hrs post-treatment, confirming that in vivo inhibition of CDKs was achieved, but recovery of Mcl-1 at 24 hrs was observed in all 4 pts, suggesting that inhibition was lost at 24 hrs. Decline in p-Rb was observed in 1 pt, while 2 pts had almost undetectable p-Rb levels at baseline. Conclusion: Dinaciclib showed anti-leukemia activity in this heavily pre-treated patient population. TLS was a notable toxicity, but was manageable in most pts with aggressive prophylaxis, monitoring and treatment. Early blast recovery and short duration of nadir observed on this study, combined with PK data showing a short t1/2 (1.5-3.3 hours) for dinaciclib and PD data demonstrating rapid reexpression of Mcl-1, support either use of longer infusion schedules (currently explored in solid tumors) or more frequent drug administration. Further exploration of dinaciclib dose and schedules in AML and ALL is planned. Disclosures: Gojo: Merck & Co.: Research Funding. Off Label Use: SCH 727965 (dinaciclib) is an investigational drug. Padmanabhan:Schering-Plough: Consultancy; Merck & Co.: Research Funding. Small:Merck & Co.: Employment, Equity Ownership. Zhang:Merck & Co.: Employment. Sadowska:Merck & Co.: Research Funding. Bannerji:Merck & Co.: Employment, Equity Ownership.

Description: Abstract 1396 Patients with relapsed or refractory CLL have limited treatment options, especially those with bulky lymph nodes. Dinaciclib is a potent and selective inhibitor of the cyclin dependent kinases CDK 1, 2, 5, and 9, and has potent anti-leukemic activity against CLL cells in ex vivo assays (LC50 of 240 nM). A phase 1 trial of dinaciclib administered by 2-hour i.v. infusion on days 1, 8 and 15 of a 28-day cycle was undertaken in CLL patients as an amendment to a now completed phase I solid tumor study. Thirty-three CLL subjects were enrolled in 5 dose cohorts including 16 subjects enrolled at the maximally tolerated dose of 14 mg/m2. The enrolled patients have a median age of 62 (range 43–79), 60% are Rai stage 3 or 4, 54% have bulky disease and 58% have high risk cytogenetics (del 17p13, del 11q22, or 〉 2 abnormalities). The median number of prior therapies are 4 (range 1–12), 88% received prior fludarabine. The starting dose of dinaciclib in CLL patients was 5 mg/m2 with subsequent cohort escalation to 7, 10, 14 and 17 mg/m2. The maximum administered dose was 17 mg/m2 where dose limiting toxicities occurred in 2 of 3 patients treated. These toxicities included a bacterial pneumonia in one patient and tumor lysis syndrome requiring temporary hemodialysis in a second patient. Expansion of the 14 mg/m2 dose level to 16 patients occurred with one additional case of TLS requiring temporary dialysis observed on Cycle 1, Day 1. In total, there were 5 cases of TLS, 3 cases of Grade 3 TLS in addition to 2 cases of TLS requiring dialysis. Common treatment related adverse events include anemia, neutropenia, thrombocytopenia, hyperglycemia, hypocalcemia, diarrhea, hypokalemia, increased AST/ALT and fatigue. Two deaths occurred on study (one each progressive disease and sepsis). The median number of treatment cycles given is 3 (range 1 – 13) with 8 patients continuing treatment for 6 cycles, 5 continuing for 9 cycles, and 4 continuing for 12 cycles. Clinical response as assessed by the 1996 NCI-WG CLL criteria (physical exam and CT evaluation) currently includes 8 partial responses out of 23 evaluable patients, including one patient proceeding to an allogeneic stem cell transplant. Ten additional patients are early in treatment (2-3 cycles administered) but are not yet evaluable for response. Responses have been observed at all dose levels studied, and include both early (at 2 cycles) and late (at 6 cycles) responses. A decrease in tumor volume has occurred in 17 patients (including responders) and additional responses may be expected with further ongoing treatment. In addition to responders, the majority of patients with proliferative disease at study entry achieved disease stabilization with acceptable toxicity while on dinaciclib treatment. Western blot assay for MCL-1 protein levels confirms pharmacodynamic activity with 10 of 10 patient samples showing a rapid decrease in MCL-1 protein levels. Further optimization of the treatment regimen will examine if less initial biochemical tumor lysis occurs with stepped up dosing of dinaciclib 10 mg/m2 in week 1 followed by 14 mg/m2 in week 2 and thereafter. Results will be updated at the meeting. Dinaciclib demonstrates promising clinical responses and feasibility of prolonged administration in heavily pre-treated CLL patients with bulky disease. These data support further study of dinaciclib in CLL and related B-cell malignancies. Disclosures: Off Label Use: SCH 727965 (dinaciclib) is an investigational drug. Small:Merck & Co.: Employment, Equity Ownership. Statkevich:Merck & Co.: Employment, Equity Ownership. Bannerji:Merck & Co.: Employment, Equity Ownership.

Description: Abstract 3966 Background: Dinaciclib (SCH 727965) is a potent and selective inhibitor of the cyclin dependent kinases CDKs 1, 2, 5, and 9, with in vitro activity against lymphoma. Methods: A phase 1 trial of dinaciclib administered by 2-hour i.v. infusion on days 1, 8 and 15 of a 28-day cycle was undertaken in solid tumor patients with 12 mg/m2 established as the recommended phase 2 dose (RPTD). The RPTD was explored in expansion cohorts of up to 10 patients each with low grade lymphomas (primarily follicular lymphoma (FL)), and intermediate/high grade lymphomas (diffuse large B-cell lymphoma (DLBCL)). Sixteen patients have been treated with dinaciclib, including 7 with FL, 1 with mantle cell lymphoma (MCL) and 1 with marginal zone lymphoma (MZL) in the low grade group and 7 with DLBCL in the intermediate/high grade group. Patient median age was 66 (range 43–82) and the median number of prior therapies was 2.5 (range 1–8). All patients received prior rituximab and 4 patients had previously received flavopiridol. All patients were treated with dinaciclib at the 12 mg/m2 dose. Dose de-escalation to 10 mg/m2 was required in 2 patients during treatment. The median number of cycles administered was 3 (range 1–9) with 3 patients continuing treatment for 3 cycles, 4 for 6 cycles, and 1 for 9 cycles. Of the 16 lymphoma patients treated, 2 remain on treatment. Response: Responses were assessed using the revised Cheson criteria for lymphoma (J Clin Oncol 25: 579-86, 2007). One partial response in a patient with DLBCL was observed with an 85% decrease in tumor mass. This patient, previously treated with R-CHOP from May-August 2008 and R-ICE from December 2008-March 2009, was able to continue on to autologous stem cell transplantation for potential curative salvage. Activity not meeting criteria for partial response was seen in 2 patients with FL (decreased tumor mass of 27% and 39%, respectively) and one patient with MCL (8% decrease in tumor mass). Toxicity: Treatment-related adverse events occurring in ≥ 25% of pts included anemia, cytokine release syndrome, nausea, vomiting, diarrhea, fatigue, leucopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common CTCAE v3.0 treatment-related grade 3 and 4 toxicities, occurring in 3 or more patients, were leukopenia, lymphopenia, and neutropenia. Cytokine release syndrome was observed in 4 patients, was manageable with dexamethasone and did not prevent continued treatment on protocol. Conclusion: Dinaciclib demonstrates clinical responses in heavily pre-treated lymphoma patients supporting further study in lymphoma and other hematologic malignancies. Updated information with longer follow-up will be presented. Disclosures: Off Label Use: SCH 727965 is an investigational drug. Small:Merck & Co.: Employment, Equity Ownership. Statkevich:Merck & Co.: Employment, Equity Ownership. Bannerji:Merck & Co: Employment, Equity Ownership.